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Month: October 2021

Chatbot for addressing COVID-19 vaccine hesitancy

Posted on by Graziella Cara

ordinateurResearchers from the CNRS, INSERM, and ENS-PSL show that such an interface is indeed capable of swaying the vaccine-hesitant. © seth schwiet on Unsplash

 

  • A considerable fraction of the population is reluctant to get vaccinated against COVID-19.
  • French scientists have designed a chatbot that offers personalised responses to questions posed by the curious or hesitant—and have demonstrated its effectiveness.

What if a few minutes of interaction with a chatbot could effectively address vaccine concerns? In an article published in the Journal of Experimental Psychology: Applied (28 October 2021), researchers from the CNRS, INSERM, and ENS-PSL show that such an interface is indeed capable of swaying the vaccine-hesitant.

Vaccine hesitancy is one of the major challenges in containing the COVID-19 pandemic. Previous studies have revealed that mass communication—through short messages relayed by television or radio—is not a very effective means of persuading the hesitant. In contrast, discussing your particular concerns with an expert whom you trust can be more persuasive, but having a face-to-face talk with every vaccine-hesitant individual is impractical.

To overcome this problem, a team of cognitive scientists from the Institut Jean-Nicod (CNRS / ENS-PSL) and the Laboratoire de Neurosciences Cognitives et Computationnelles (INSERM / ENS-PSL) created a chatbot that provides users with answers to 51 common questions about COVID-19 vaccines.1

Chatbots have the advantage of offering quick, personalized Q and A sessions while reaching a large number of people.

The team tested their chatbot with 338 individuals and compared their reactions to those of a control group of 305 participants who only read a brief paragraph that gave information about COVID-19 vaccines. After a few minutes of interaction with the chatbot, the number of participants with positive views of vaccination increased by 37%. People were also more open to getting vaccinated after using the chatbot: declarations of vaccine refusal fell 20%. Such changes in attitude were negligible in the control group.

It remains to be shown whether the effects of chatbot interaction are lasting, and whether they are the same across age groups, and among those most resistant to vaccination.2

Nevertheless, this study has demonstrated that a chatbot can indirectly reach a very large audience: half of the experimental group later tried to persuade others to get vaccinated, with three-quarters of them stating they drew on information provided by the chatbot to do so.

These findings suggest that a chatbot regularly updated to reflect the latest vaccine science could be an effective tool to help reduce vaccine hesitancy.

 

Notes

1The questions were selected on the basis of surveys on reasons for vaccine hesitancy as well as articles about vaccine-related preconceptions. Their answers were prepared from scientific sources and approved by COVID-19 vaccine specialists.

2On average, the group of participants was younger and more educated than the overall population.

COVID-19: How Does SARS-CoV-2 Infection Affect Vascular Irrigation of the Brain?

Posted on by Graziella Cara

tissu cérébral humain post-mortem

Fluorescent image of post-mortem human brain tissue showing cell nuclei (blue) that reveal a blood vessel in which the vascular endothelial cells express the genetic material of SARS-CoV-2 (red). © Vincent Prévot/Inserm

 

A large number of researchers are currently mobilized to increase knowledge of SARS-CoV-2 in order to improve the treatment of infected patients and try to predict the future health impacts of infection with the virus. As part of an international collaboration, researchers from Inserm, Université de Lille, Lille University Hospital, and Pasteur Institute Lille within the Lille Neuroscience & Cognition laboratory, along with their colleagues from the CNRS1, have been the first to identify a direct effect of SARS-CoV-2 on the brain’s blood vessels. Certain cells, namely the cerebral vascular endothelial cells – essential components of the blood-brain barrier that protects the brain – are affected by a phenomenon of cell death. These findings, published in the journal Nature Neuroscience, particularly question the long-term impacts of the disease.

The blood vessels are comprised of endothelial cells. These include the vascular endothelial cells in the brain that make up the blood-brain barrier (BBB). The primary function of the BBB is to isolate the central nervous system from the bloodstream, preventing foreign substances or potentially toxic molecules from entering the brain and spinal cord while allowing the transfer of nutrients essential to their activity. As part of this effort, the vascular endothelial cells in the brain therefore play a key role in the proper irrigation of the organ, with their survival being essential for it to function correctly.

Within the framework of an international collaboration funded by the European Research Council3, the authors of the study looked at the vascular endothelial cells of the brain and the consequences of SARS-CoV-2 infection on their functioning.

Using preclinical research models and also by studying the cortex of patients who died as a result of SARS-CoV-2 infection, the researchers have shown that infection leads to the death of endothelial cells in the brain, resulting in the appearance of “ghost vessels” in the brain (empty tubes with no endothelial cells).

As a result, these essential cells can no longer perform their function in the BBB.

How does this endothelial cell death occur? What are the mechanisms involved? Thanks to state-of-the-art techniques2, the team has discovered that SARS-CoV-2 generates the manufacturing, from its own genetic material, of molecular scissors by the endothelial cells it infects. These scissors cleave a protein called NEMO which, being necessary for the endothelial cells to survive, therefore leads to their death.

 

The impacts of endothelial cell death on brain function

According to the scientists, the death of vascular endothelial cells in the brain can have two major consequences:

  • A temporary rupture of the BBB causing microbleeds in regions where the blood is not meant to have free access.
  • Hypoperfusion of some brain regions (due to the presence of non-functional ghost vessels), which is a decrease in blood flow that in the most serious cases can be fatal.

However, the study shows that the situation is reversible.

Furthermore, the scientists are interested in the long-term impacts of this phase of vulnerability during which brain irrigation is decreased. According to them, even if this hypothesis remains to be verified, this window of time could predispose certain people with the disease to develop cognitive or neurodegenerative disorders, or even dementia.

“This awareness of the severity of SARS-CoV-2 infection and its impacts on proper brain function is vital to enable the best possible management of infected patients in the years to come,” concludes Vincent Prévot, Inserm Research Director.

 

1 At the Center for Infection and Immunity of Lille (CNRS/Inserm/Institut Pasteur Lille/Université de Lille/Lille University Hospital)

2 Such as transgenesis, single-cell RNA sequencing, mass spectrometry and super-resolution microscopy.

3 Program funded by the European Research Council (ERC Synergy), with the participation of Drs. Prévot (Inserm, France), Nogueiras (University of Santiago de Compostela, Spain), and Schwaninger (University of Lübeck, Germany).

Découverte de nouveaux marqueurs génétiques à l’origine d’une maladie des artères essentiellement féminine

Posted on by Graziella Cara

Towards the elimination of cholera in Haiti

Posted on by Graziella Cara

robinet eau

Favored by poor access to clean water, sanitation, and hygiene, disease transmission has persisted in epidemic waves © Unsplash

In 2013, a medical team from the AP-HP, Sorbonne University, Inserm, the European Hospital of Marseille, the IRD, Aix-Marseille University (SESSTIM) and the AP- HM proposed to the Haitian government and to Unicef ​​a coordinated strategy to fight against cholera, aimed at breaking the chains of transmission. 

This strategy and its results, which show the apparent cessation of cholera transmission in Haiti since 2019, have just been the subject of a publication in the journal Emerging Infectious Diseases.

Unfortunately imported into Haiti in 2010 during a movement of troops from Asia, cholera caused in this Caribbean country one of the most violent epidemics of recent decades. Favored by poor access to safe drinking water, sanitation and hygiene, the transmission of the disease has persisted in epidemic waves to such an extent that the elimination of cholera in the country has been considered impossible by many. .

In 2013, a medical team from the AP-HP, Sorbonne University, Inserm, the European Hospital of Marseille, the IRD, Aix-Marseille University (SESSTIM) and the AP- HM proposed to the Haitian government and to Unicef ​​a coordinated strategy to fight against cholera, aimed at breaking the chains of transmission.

Mobile rapid response teams have thus carried out more than 50,000 interventions throughout the country in order to raise awareness, distribute water and hygiene treatment kits, and often “minute” antibiotic prophylaxis to contact subjects of patients received in the hospital. health centers.

In collaboration with the Haitian Ministry of Health, this medical team has just shown, in an article entitled ”  Towards cholera elimination in Haiti  ” that there is no longer the slightest sign of activity of the epidemic since February 2019 despite intense microbiological research.

These dramatic results suggest that case area targeted interventions led by rapid response teams have played a key role. They also question the theory that the bacteria responsible for the disease would persist in the country’s aquatic environments, preventing its elimination.

Study on the role of “ceramides” in infection by SARS-CoV-2 which could constitute a biomarker of severity and a therapeutic target in the management of Covid-19

Posted on by Graziella Cara

 

SARS-CoV-2

Electron microscopy of a cell infected with SARS-CoV-2 © Philippe Roingeard, Anne Bull-Maurer, Sonia Georgeault, unité Inserm U1259 MAVIVH & Université de Tours, France.

 

Teams from the psychiatry and addictology department of the Corentin-Celton AP-HP hospital, the University of Paris and Inserm in collaboration with the University of Erlangen-Nuremberg and the University of Duisburg-Essen , coordinated by Dr Nicolas Hoertel, Prof Jo hannes Kornhuber and Prof Erich Gulbins, published on October 4, 2021 in the journal Molecular Psychiatry (Nature Publishing Group) a summary of the results of the international literature on the central role that “ ceramides ”, a class of lipids, may play a role in SARS-CoV-2 infection.

Results from in vitro data [1, 2] indicate that an enzyme found in cell lysosomes, acid sphingomyelinase (ASM), is activated by the virus upon binding to its ACE-2 cell receptor, inducing synthesis of a specific class of lipids, the “ceramides”, in the membrane of cells. These studies [1, 2] demonstrate that these ceramides serve as a gateway for the virus to infect cells.

Indeed, the reduction in the quantity of ceramides by functional inhibitors of ASM (called FIASMA, comprising in particular certain antidepressants such as fluoxetine or else fluvoxamine) or the use of anti-ceramide antibodies make it possible to greatly reduce infection in vitro according to these same studies [1-2] .

In addition, clinical data [3, 4] indicate that elevated plasma levels of ceramides are significantly and strongly associated with the clinical severity of infection and the severity of inflammation in patients with Covid-19.

Finally, preclinical [1, 2, 5, 6] , observational [7-9] and three clinical trials [10-12] , including two randomized placebo-controlled trials [10, 12] , conclude on potentially strong efficacy of fluvoxamine and fluoxetine against Covid-19. Several clinical trials using fluvoxamine or fluoxetine, necessary to confirm these very encouraging results, are underway in several countries (United States, Canada, South Africa, Brazil and Croatia).

This publication concludes that the activity of the enzyme ASM and the plasma levels of ceramides could allow a better understanding of this infection and its risk factors for poor prognosis, as well as the antiviral, anti-inflammatory and clinical effects observed with drugs that are functional ASM inhibitors, including fluoxetine and fluvoxamine.

 

References

  1. Carpinteiro, A. et al. Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells. Cell Rep. Med. 100142 (2020).
  2. Carpinteiro, A. et al. Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. J. Biol. Chem. 100701 (2021). doi: 10.1016 / j.jbc.2021.100701
  3. Marín-Corral J, Rodríguez-Morató J, Gomez-Gomez A, Pascual-Guardia S, Muñoz-Bermúdez R, Salazar-Degracia A, et al. Metabolic signatures associated with severity in hospitalized COVID-19 patients. Int J Mol Sci. 2021; 22: 4794.
  4. Khodadoust, M. Ceramide levels and COVID-19 respiratory distress, a causal relationship. Research Square. 2021. https://doi.org/10.21203/rs.3.rs-443020/v3 .
  5. Schloer, S. et al. Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerg. Microbes Infect. 9, 2245–2255 (2020).
  6. Zimniak M. et al. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue. Sci Rep. 2021 Mar 15; 11 (1): 5890.
  7. Hoertel, N. et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol. Psychiatry (2021) .doi: 10.1038 / s41380-021-01021-4
  8. Diez-Quevedo C et al. Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients. Acta Psychiatr Scand. 2021 Jun; 143 (6): 526-534.
  9. Hoertel, N. et al. Association between FIASMAs and reduced risk of intubation or death in individuals hospitalized for severe COVID-19: an observational multicenter study. Clin Pharmacol Ther. 2021. https://doi.org/10.1002/cpt.2317 .
  10. Lenze, EJ et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA 324, 2292–2300 (2020).
  11. Seftel, D. & Boulware, DR Prospective Cohort of Fluvoxamine for Early Treatment of Coronavirus Disease 19. Open Forum Infect. Say. 8, ofab050 (2021).
  12. Reis, G., et al. Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial. medRxiv . 2021; https://doi.org/10.1101/2021.08.19.21262323 .

Good tolerance of the BNT162b2 vaccine (Pfizer / BioNTech) and good efficacy of the immune response against SARS-CoV-2 variants in patients with systemic lupus

Posted on by Graziella Cara

vaccin anti covid

Covid vaccine © Adobe Stock

 

Teams from the immunology department and internal medicine department 2 of the Pitié-Salpêtrière AP-HP hospital, Sorbonne University and Inserm, measured the antibody and cellular responses generated by a messenger RNA vaccine in patients with systemic lupus (LS). This work, coordinated by Professors Guy Gorochov (CIMI-Paris) and Zahir Amoura (National Lupus Reference Center) shows that vaccination is both well tolerated and effective, even against worrying variants. For the first time, the factors associated with a poor vaccine response in some of these patients have been identified in order to better anticipate who should benefit from reinforced protective measures and / or adapted vaccine protocols. This work was the subjectfrom an October 4 publication in the journal Annals of Rheumatic Diseases.

Systemic lupus (LS) is a chronic autoimmune disease preferentially affecting young women. The attacks are mainly articular, cutaneous, renal, cardio-respiratory, neurological and hematological. The disease is characterized by the production of autoantibodies directed against nuclear antigens. It typically evolves in spurts. For these patients, two hypotheses were considered concerning the effects of the messenger RNA vaccination: the occurrence of more frequent adverse effects, or even the exacerbation of the disease in patients with LS, or an ineffective response to vaccination for patients with LS. patients on immunosuppressants.

The teams compared the effects of vaccination in 136 patients with systemic lupus (LS). 126 of them, who received 2 doses of the BNT162b2 vaccine (Pfizer / BioNTech) and followed the entire clinical-biological surveillance course, were included in the final analysis. The two vaccine doses were separated by 21 to 28 days with a clinical-biological evaluation from the day of the first injection and up to 42 days after it (D42). The clinical activity of the disease was measured at each visit (D0, D7-14, D21-28, D42) using standardized indices. Some patients were vaccinated while their lupus disease was active.

During the 40-day follow-up, no significant change in disease activity was observed, either in patients active at the time of vaccination, or in those who showed no signs of the disease. The only notable side effects related to the vaccination were mild or moderate pain at the injection site.

A pseudo virus expressing the envelope (Spike) of the reference SARS-CoV-2 (D614G) or that of the variants B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta ), B.1.617.3, B.1.1.28 (Gamma) and B.1.351 (Beta) was used to measure the neutralizing activity of the serum collected on D42. 82% of the patients tested were able to effectively neutralize the reference strain and the Alpha variant. As expected, a slight decrease in the neutralization efficiency of the other variants was noted, mainly for the Beta variant, neutralized by the serum of 60% of the patients tested, while the Delta variant was neutralized in 76% of cases.

At present, the vaccine response criteria are still poorly understood. Among the various treatments received against lupus, this work was able to combine methotrexate and mycophenolate mofetil, two immunosuppressive treatments, with lower rates of IgG responses to the human receptor binding domain (RBD) of SARS-CoV-2. (independently of immunosuppressive treatments). Long-term corticosteroid intake (median prednisone dose: 19 mg / day) was not, however, associated with a poor vaccine response.

This work evaluated certain therapeutic and biological criteria of vaccine response.

A decreased vaccine response, i.e. a lower level of protective antibodies, has been shown when the patient with LS is treated with methotrexate or mycophenolate mofetil (two immunosuppressive treatments). Conversely, taking corticosteroids, regularly prescribed in LS, was not associated with a poor vaccine response.

The study also looked at the immune status of patients at the start of the vaccination protocol. The level of circulating naive B lymphocytes (CD19 + CD27-IgD +) and the overall concentration of IgG antibodies on D0 were associated with a more intense vaccine response.

In conclusion, the vaccination of lupus patients with BNT162b2 is very well tolerated and its efficacy is reduced only in patients treated with methotrexate or mycophenolate mofetil. A pre-existing alteration in the adaptive humoral response is also associated with the poor vaccine response.

Lancement du portail appelsprojetsrecherche.fr

Posted on by Graziella Cara

New therapeutic perspectives for patients with lymphatic abnormalities linked to a mutation in the PIK3CA gene

Posted on by Graziella Cara

Anatomie 3d du système lymphatique © Fotalia

3d Anatomy of lymphatic system © Fotalia

 

The team of the adult nephrology-renal transplantation department of the Necker-Enfants Malades AP-HP hospital, Inserm and the University of Paris has carried out work, coordinated by Prof. Guillaume Canaud, which opens up new perspectives. therapies for patients with lymphatic abnormalities linked to a mutation in the PIK3CA gene.

The results of this study were published on October 6, 2021 in the journal Science Translational Medicine .

Lymphatic malformations, formerly called lymphangiomas, are malformations of the lymphatic system which can be localized (cutaneous, subcutaneous or mucous) or more rarely spread to the whole body. They are most often congenital and visible before the age of 2 years. They are frequently localized in the axillary and cervical regions. These malformations can be accompanied by painful “inflammatory flare-ups”, compression of organs, especially of the trachea, necessitating the installation of a tracheotomy, diffuse effusions in the pleura or serious infection. They can sometimes be life threatening. These malformations very often have a significant aesthetic impact and a strong impact on the integration of patients into society.

In the vast majority of cases, lymphatic malformations are due to a mutation in the PIK3CA gene acquired during embryonic development (in utero). Current treatments are based on percutaneous sclerosis guided by radiology and / or often decaying surgeries. They can be combined with supportive care such as corticosteroids to treat flare-ups, analgesics, antibiotics, nocturnal respiratory support, and nutritional and psychological support. In some cases, an immunosuppressive therapy, rapamycin sirolimus, is used with varying effectiveness. There is no approved treatment for this indication at this time.

The research work which has just been published in the journal Science Translational Medicine opens up new therapeutic perspectives for these patients with lymphatic abnormalities linked to a mutation in the PIK3CA gene.

New therapeutic perspectives for patients with lymphatic abnormalities linked to a mutation in the PIK3CA gene >> see the video

 

 

The team created the first mouse model carrying a mutation in the PIK3CA gene specifically in lymphatic vessels which recapitulates the different types of lymphatic malformations presented by patients. This experimental model can develop very localized or, on the contrary, very diffuse malformations, depending on the needs.

The team then identified alpelisib (BYL719), a specific inhibitor of PIK3CA, and demonstrated its role as a therapeutic molecule of interest in this preclinical model. With very promising results in animals, the researchers then treated six patients, three children and three adults, with severe lymphatic malformations secondary to a PIK3CA mutation, who had resisted conventional treatments. 

In six months, treatment with alplesib was accompanied by an improvement in patients’ symptoms (pain, inflammatory flare-ups, oozing, discomfort on swallowing, etc.) and a 48% reduction in the volume of malformations measured by MRI. As previously reported in another indication, the treatment was well tolerated.

This work, thanks to the new experimental model created, makes it possible to better understand the pathophysiology of lymphatic malformations but above all opens up new very promising therapeutic perspectives.

This research work was supported by:

-European Research Council (CoG 2020 grant number 101000948 and PoC-2016 grant number 737546)

-National Research Agency – Future Investments Program (ANR-18-RHUS-005)

-National Research Agency – Collaborative Research Program (19-CE14-0030-01).

-CLOVES SYNDROME COMMUNITY (West Kennebunk, USA)

-Emmanuel BOUSSARD Foundation (London, UK)

-DAY SOLVAY Foundation (Paris, France) TOURRE Foundation (Paris, France)

-BETTENCOURT SCHUELLER Foundation (Paris, France)

-Foundation Simone and Cino DEL DUCA (Paris, France)

-Foundation Line RENAUD-Loulou GASTE (Paris, France)

– Schlumberger Foundation for Education and Research (Paris, France)

-Inserm

-Assistance Publique Hôpitaux de Paris

-University of Paris

-And many other generous donors

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